This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1nwq
From Proteopedia
OCA (Talk | contribs)
(New page: 200px<br /><applet load="1nwq" size="450" color="white" frame="true" align="right" spinBox="true" caption="1nwq, resolution 2.80Å" /> '''CRYSTAL STRUCTURE OF...)
Next diff →
Revision as of 20:29, 20 November 2007
|
CRYSTAL STRUCTURE OF C/EBPALPHA-DNA COMPLEX
Overview
CCAAT/enhancer-binding proteins (C/EBPs) are basic region leucine zipper, (bZIP) transcription factors that regulate cell differentiation, growth, survival, and inflammation. To understand the molecular basis of DNA, recognition by the C/EBP family we determined the x-ray structure of a, C/EBPalpha bZIP polypeptide bound to its cognate DNA site, (A(-5)T(-4)T(-3)G(-2)C(-1)G(1)C(2)A(3)A(4)T(5)) and characterized several, basic region mutants. Binding specificity is provided by interactions of, basic region residues Arg(289), Asn(292), Ala(295), Val(296), Ser(299), and Arg(300) with DNA bases. A striking feature of the C/EBPalpha, protein-DNA interface that distinguishes it from known bZIP-DNA complexes, is the central role of Arg(289), which is hydrogen-bonded to base A(3), phosphate, Asn(292) (invariant in bZIPs), and Asn(293). The conformation, of Arg(289) is also restricted by Tyr(285). In accordance with the, structural model, mutation of Arg(289) or a pair of its interacting, partners (Tyr(285) and Asn(293)) abolished C/EBPalpha binding activity., Val(296) (Ala in most other bZIPs) contributes to C/EBPalpha specificity, by discriminating against purines at position -3 and imposing steric, restraints on the invariant Arg(300). Mutating Val(296) to Ala strongly, enhanced C/EBPalpha binding to cAMP response element (CRE) sites while, retaining affinity for C/EBP sites. Thus, Arg(289) is essential for, formation of the complementary protein-DNA interface, whereas Val(296), functions primarily to restrict interactions with related sequences such, as CRE sites rather than specifying binding to C/EBP sites. Our studies, also help to explain the phenotypes of mice carrying targeted mutations in, the C/EBPalpha bZIP region.
About this Structure
1NWQ is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.
Reference
Structural basis for DNA recognition by the basic region leucine zipper transcription factor CCAAT/enhancer-binding protein alpha., Miller M, Shuman JD, Sebastian T, Dauter Z, Johnson PF, J Biol Chem. 2003 Apr 25;278(17):15178-84. Epub 2003 Feb 10. PMID:12578822
Page seeded by OCA on Tue Nov 20 22:36:54 2007
